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1.
Biol. Res ; 51: 10, 2018. tab, graf
Article in English | LILACS | ID: biblio-950896

ABSTRACT

PROPOSE: We aimed to explore the potential molecular mechanism and independent prognostic genes for colon cancer (CC). METHODS: Microarray datasets GSE17536 and GSE39582 were downloaded from Gene Expression Omnibus. Meanwhile, the whole CC-related dataset were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNA (DEMs) were identified between cancer tissue samples and para-carcinoma tissue samples in TCGA dataset, followed by the KEGG pathway and GO function analyses. Furthermore, the clinical prognostic analysis including overall survival (OS) and disease-free survival (DFS) were performed in all three datasets. RESULTS: A total of 633 up- and 321 down-regulated mRNAs were revealed in TCGA dataset. The up-regulated mRNAs were mainly assembled in functions including extracellular matrix and pathways including Wnt signaling. The down-regulated mRNAs were mainly assembled in functions like Digestion and pathways like Drug metabolism. Furthermore, up-regulation of UL16-binding protein 2 (ULBP2) was associated with OS in CC patients. A total of 12 DEMs including Surfactant Associated 2 (SFTA2) were potential DFS prognostic genes in CC patients. Meanwhile, the GRP and Transmembrane Protein 37 (TMEM37) were two outstanding independent DFS prognostic genes in CC. CONCLUSIONS: ULBP2 might be a potential novel OS prognostic biomarker in CC, while GRP and TMEM37 could be served as the independent DFS prognostic genes in CC. Furthermore, functions including extracellular matrix and digestion, as well as pathways including Wnt signaling and drug metabolism might play important roles in the process of CC.


Subject(s)
Humans , Animals , Colonic Neoplasms/diagnosis , Colonic Neoplasms/genetics , Gene Expression Profiling/methods , RNA, Messenger/genetics , RNA, Messenger/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Genetic Markers , Down-Regulation/genetics , Gene Expression Regulation, Neoplastic , Up-Regulation/genetics , Risk Factors , Colonic Neoplasms/metabolism , Disease-Free Survival , Gastrin-Releasing Peptide/genetics , Gastrin-Releasing Peptide/metabolism , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Pulmonary Surfactant-Associated Protein A/genetics , Pulmonary Surfactant-Associated Protein A/metabolism , Microarray Analysis , Murinae , Kaplan-Meier Estimate , GPI-Linked Proteins/genetics , GPI-Linked Proteins/metabolism
2.
Chinese Medical Journal ; (24): 1236-1243, 2017.
Article in English | WPRIM | ID: wpr-330638

ABSTRACT

<p><b>BACKGROUND</b>Surfactant protein-A (SP-A) contributes to the regulation of sepsis-induced acute kidney injury. In a previous study, we demonstrated that the expression of SP-A in the human renal tubular epithelial (HK-2) cells can be stimulated by lipopolysaccharide (LPS). The present study evaluated the possible signal-transducing mechanisms of LPS-induced SP-A biosynthesis in the HK-2 cells.</p><p><b>METHODS</b>Tetrazolium salt colorimetry (MTT) assay was used to detect cell viability of HK-2 cells after LPS stimulation on different time points. HK-2 cells were stimulated with 100 ng/ml of LPS for different durations to determine the effects of LPS on SP-A and toll-like receptor 4 (TLR4) messenger RNA (mRNA) expression, as well as phosphorylation of mitogen-activated/extracellular signal-regulated kinase (MEK) 1, extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38MAPK), and nuclear factor-kappa B (NF-κB) inhibitor-alpha (IkB-α). Then, HK-2 cells were pretreated with CLI-095, a TLR4 inhibitor, to analyze mRNA and protein levels of SP-A and TLR4 and expression of NF-κB in the cytoplasm and nucleus of HK-2 before LPS exposure.</p><p><b>RESULTS</b>HK-2 cells exposed to 100 ng/ml of LPS for 1, 6, and 24 h did not affect cell viability which showed no toxic effect of 100 ng/ml LPS on cells (P = 0.16); however, the biosynthesis of SP-A mRNA and protein in HK-2 cells was significantly increased (P = 0.02). As to the mechanism, LPS enhanced transmembrane receptor TLR4 protein expression. Sequentially, LPS time dependently augmented phosphorylation of MEK1, ERK1/2, and p38MAPK. In addition, levels of phosphorylated IκB-α and nuclear NF-κB were augmented with LPS exposure for 2 h. LPS-induced SP-A and TLR4 mRNA as well as NF-κB expression were significantly inhibited by pretreatment with CLI-095.</p><p><b>CONCLUSIONS</b>The present study exhibited that LPS can increase SP-A synthesis in human renal epithelial cells through sequentially activating the TLR4-related MEK1-ERK1/2-NF-κB-dependent pathway.</p>


Subject(s)
Cell Line , Cell Survival , Physiology , Colorimetry , Humans , Kidney , Cell Biology , Metabolism , Lipopolysaccharides , Toxicity , Mitogen-Activated Protein Kinase 1 , Metabolism , Mitogen-Activated Protein Kinase 3 , Metabolism , NF-kappa B , Metabolism , Pulmonary Surfactant-Associated Protein A , Metabolism , Sulfonamides , Pharmacology , Tetrazolium Salts , Chemistry , Toll-Like Receptor 4 , Metabolism
3.
Article in English | WPRIM | ID: wpr-56121

ABSTRACT

This study explored the relationship between the fractional exhaled nitric oxide (FeNO) level and the efficacy of inhaled corticosteroid (ICS) in asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) patients with different disease severity. A total of 127 ACOS patients with ACOS (case group) and 131 healthy people (control group) were enrolled in this study. Based on the severity of COPD, the ACOS patients were divided into: mild ACOS; moderate ACOS; severe ACOS; and extremely severe ACOS groups. We compared FeNO levels, pulmonary function parameters including percentage of forced expiratory volume in 1 second (FEV1) to predicted value (FEV1%pred), ratio of FEV1 to forced vital capacity (FEV1/FVC), inspiratory capacity to total lung capacity (IC/TLC) and residual volume to total lung capacity (RV/TLC), arterial blood gas parameters, including PH, arterial partial pressure of oxygen (PaO₂) and arterial partial pressure of carbon dioxide (PaCO₂), total serum immunoglobulin E (IgE), induced sputum eosinophil (EOS), plasma surfactant protein A (SP-A), plasma soluble receptor for advanced glycation end products (sRAGE), sputum myeloperoxidase (MPO), sputum neutrophil gelatinase-associated lipocalin (NGAL) and Asthma Control Test (ACT) scores, and COPD Assessment Test (CAT) scores. Compared with pre-treatment parameters, the FeNO levels, RV/TLC, PaCO₂, total serum IgE, induced sputum EOS, plasma SP-A, sputum MPO, sputum NGAL, and CAT scores were significantly decreased after 6 months of ICS treatment, while FEV1%pred, FEV1/FVC, IC/TLC, PH, PaO₂, plasma sRAGE, and ACT scores were significantly increased in ACOS patients with different disease severity after 6 months of ICS treatment. This finding suggests that the FeNO level may accurately predict the efficacy of ICS in the treatment of ACOS patients.


Subject(s)
Animals , Asthma , Carbon Dioxide , Cats , Eosinophils , Forced Expiratory Volume , Glycation End Products, Advanced , Humans , Hydrogen-Ion Concentration , Immunoglobulin E , Immunoglobulins , Inspiratory Capacity , Lipocalins , Lung Diseases, Obstructive , Neutrophils , Nitric Oxide , Oxygen , Partial Pressure , Peroxidase , Plasma , Pulmonary Disease, Chronic Obstructive , Pulmonary Surfactant-Associated Protein A , Residual Volume , Sputum , Total Lung Capacity , Vital Capacity
4.
Article in Chinese | WPRIM | ID: wpr-261223

ABSTRACT

<p><b>OBJECTIVE</b>To observe the levels of pulmonary surfactant proteins A and D (SP-A, SP-D) in bronchoalveolar lavage fluid (BALF) of children with pneumonia, and to explore their relationships with clinical characteristics.</p><p><b>METHODS</b>Thirty-five children with pneumonia were enrolled in this study. Differential cell counts were obtained by Countstar counting board. The levels of SP-A and SP-D in BALF were detected using ELISA.</p><p><b>RESULTS</b>In children with pneumonia, SP-D levels were significantly higher than SP-A levels (P<0.001). SP-D levels were negatively correlated with the neutrophil percentage in BALF (r(s)=-0.5255, P<0.01). SP-D levels in BALF in children with increased blood C-reactive protein levels (>8 mg/L) were significantly lower than in those with a normal level of C-reactive protein (P<0.05). Compared with those in children without wheezing, SP-D levels in children with wheezing were significantly lower (P<0.01). There was no correlation between SP-A levels and clinical characteristics.</p><p><b>CONCLUSIONS</b>SP-D levels in BALF are significantly higher than SP-A levels, and have a certain correlation with clinical characteristics in children with pneumonia. As a protective factor, SP-D plays a more important role than SP-A in regulating the immune and inflammatory responses.</p>


Subject(s)
Bronchoalveolar Lavage Fluid , Chemistry , C-Reactive Protein , Child , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Female , Humans , Infant , Male , Pneumonia , Metabolism , Pulmonary Surfactant-Associated Protein A , Pulmonary Surfactant-Associated Protein D
5.
Article in English | WPRIM | ID: wpr-296565

ABSTRACT

Silicosis is one of the most serious occupational diseases in China and dates back to centuries ago. In this study, we successfully established a rat model of silicosis by intratracheal silica injection for 28 days and determined hydroxyproline levels to evaluate collagen metabolism in lung homogenates. Oxidative stress status was evaluated by detecting catalase and glutathione peroxidase activities. Expression levels of peroxiredoxins (Prx I and Prx VI) were detected by Western blotting. Pulmonary surfactant protein A (SP-A) levels in rat serum and lung tissue were analyzed by ELISA, and SP-A and Prx expression levels in lung tissues were detected by immunohistochemistry. The results suggest that Prx proteins may be involved in pulmonary fibrosis induced by silica. Downregulation of SP-A expression caused due to silica is an important factor in the occurrence and development of silicosis.


Subject(s)
Animals , Disease Models, Animal , Humans , Lung , Metabolism , Male , Oxidative Stress , Peroxiredoxin VI , Genetics , Metabolism , Peroxiredoxins , Genetics , Metabolism , Pulmonary Surfactant-Associated Protein A , Genetics , Metabolism , Rats , Silicon Dioxide , Toxicity , Silicosis , Genetics , Metabolism
6.
Acta cir. bras ; 29(9): 573-578, 09/2014. tab, graf
Article in English | LILACS | ID: lil-722124

ABSTRACT

PURPOSE: To evaluate surfactant protein A levels in an hepatopulmonary syndrome rat model. To date, there have been no studies aimed at evaluating surfactant levels in the setting of cirrhosis or hepatopulmonary syndrome. METHODS: A total of 35 rats were divided into control, sham, and experimental HPS groups. We evaluated surfactant protein A levels in rats and the experimental model designed to induce hepatopulmonary syndrome was common bile duct ligation. Statistical analysis was performed using GraphPad Prism Software(r). Differences were considered statistically significant when p<0.05. RESULTS: Lung homogenate of surfactant protein A levels were lower in the experimental hepatopulmonary syndrome and sham groups in comparison to the control group (p<0.05). Serum SP-A levels were the same in experimental hepatopulmonary syndrome and control groups but decreased in the sham group compared with the experimental groups (p<0.05). Myeloperoxidase activity was higher in the experimental hepatopulmonary syndrome group than the other two groups (p<0.05). CONCLUSION: Surfactant protein A is present in experimental hepatopulmonary syndrome and leads to an imbalance between serum and pulmonary levels due to systemic inflammatory response. .


Subject(s)
Animals , Male , Disease Models, Animal , Hepatopulmonary Syndrome/metabolism , Lung/metabolism , Pulmonary Surfactant-Associated Protein A/metabolism , Blood Gas Analysis , Common Bile Duct , Hepatopulmonary Syndrome/pathology , Ligation , Peroxidase/metabolism , Pulmonary Surfactant-Associated Protein A/analysis , Rats, Wistar , Reference Values
7.
Article in English | WPRIM | ID: wpr-351075

ABSTRACT

Alveolar epithelial type II (AT II) cells are essential for lung development and remodeling, as they are precursors for type I cells and also produce other non-repair cells (fibroblasts). Progenitor cells are believed to possess capability of multi-potent transdifferentiation, which is closely related to the niche, suggesting the importance of establishment of a lung progenitor cell niche model. We hypothesized that pulmonary surfactant-associated protein A (SPA) suicide gene system would cause AT II cell to kill itself through apoptosis and leave its niche. In vitro, the recombinant adeno-associated virus vectors-SPA-thymidine kinase (rAAV-SPA-TK) system was established to get targeted apoptotic AT II cells. The apoptosis of AT II cells was detected by using MTT. The results showed that cloned SPA gene promoter had specific transcriptional activity in SPA high expression cells, and SPA high expression cells (H441) transfected with TK gene had higher sensitivity to ganciclovir (GCV) than SPA low expression cells (A549). In vivo, increased apoptosis of AT II cells induced by GCV in rAAV-SPA-TK system was observed by TUNEL. Finally, the successful packaging and application of rAAV-SPA-TK system provide experimental basis to get specific lung progenitor cell (AT II) niche in vitro and in vivo.


Subject(s)
Antiviral Agents , Pharmacology , Apoptosis , Cell Line, Tumor , Cell Survival , Cells, Cultured , Dependovirus , Genetics , Dose-Response Relationship, Drug , Electrophoresis, Polyacrylamide Gel , Epithelial Cells , Cell Biology , Metabolism , Ganciclovir , Pharmacology , Gene Expression Regulation, Neoplastic , Genes, Transgenic, Suicide , Genetics , Genetic Vectors , Genetics , Humans , In Situ Nick-End Labeling , Luciferases , Genetics , Metabolism , Promoter Regions, Genetic , Genetics , Pulmonary Alveoli , Cell Biology , Metabolism , Pulmonary Surfactant-Associated Protein A , Genetics , Metabolism , Thymidine Kinase , Genetics , Metabolism
8.
Chinese Medical Journal ; (24): 343-347, 2014.
Article in English | WPRIM | ID: wpr-317990

ABSTRACT

<p><b>BACKGROUND</b>Surfactant protein A (SP-A) contributes to the regulation of sepsis-induced acute lung injury. In a previous study, we demonstrated the expression and localization of SP-A in the kidneys. The present study evaluated the effect of SP-A on lipopolysaccharide (LPS)-induced tumor necrosis factor-a (TNF-α) expression and its underlying mechanisms in the human renal tubular epithelial (HK-2) cells.</p><p><b>METHODS</b>Indirect immunofluorescence assay was used to detect SP-A distribution and expression in HK-2 cells. HK-2 cells were treated with various concentrations of LPS (0, 0.1, 1, 2, 5, and 10 mg/L) for 8 hours and with 5 mg/L LPS for different times (0, 2, 4, 8, 16, and 24 hours) to determine the effects of LPS on SP-A and TNF-α expression. Then, HK-2 cells were transfected with SP-A siRNA to analyze nuclear factor κB (NF-κB) P65 and TNF-α expression of HK-2 cells after LPS-treatment.</p><p><b>RESULTS</b>Indirect immunofluorescence assay revealed that SP-A is localized to the membrane and cytoplasm of HK-2 cells. Interestingly, SP-A1/SP-A2 and TNF-a expression were found to be significantly increased in HK-2 cells upon LPS treatment. Transfection of LPS-treated HK-2 cells with SP-A siRNA resulted in significant increases in the levels of NF-κB P65 protein and TNF-α mRNA and protein compared to those in non-transfected LPS-treated HK-2 cells.</p><p><b>CONCLUSION</b>SP-A plays an important role in protecting cells against sepsis-induced acute kidney injury by inhibiting NF-κB activity to modulate LPS-induced increase in TNF-α expression.</p>


Subject(s)
Cell Line , Epithelial Cells , Cell Biology , Metabolism , Fluorescent Antibody Technique, Indirect , Humans , Kidney Tubules, Proximal , Cell Biology , Lipopolysaccharides , Pharmacology , Pulmonary Surfactant-Associated Protein A , Metabolism , Pharmacology , Tumor Necrosis Factor-alpha , Metabolism
9.
Article in Chinese | WPRIM | ID: wpr-815500

ABSTRACT

OBJECTIVE@#To determine the influence of different stimulation of abdominal operation on lung.@*METHODS@#We randomly divided 100 SD male rats into 5 groups(n=20): An anesthesia control group (Group A), an abdominal skin 2 cm incision group (Group B), an abdominal skin+ muscle 2 cm incision group (Group C ), an abdominal skin+muscle+peritoneum 2 cm incision group (Group D), and an abdominal skin+muscle+peritoneum 2 cm incision+2 min laparoscopy in abdomen+pull exploration bowel group (Group E). Propofol was used for induction of anaesthesia by rat tail vein with 10 mg/kg, with 35-45 mg/(kg.h) during the operation. Anesthesia depth was maintained during moderate sedation without obvious analgesia action level. According to the postoperative specimens at different time, each group was divided into 4 sub groups, including 6-hour group, 1-day group, 3-day group, and 7-day group(n=5). Immunohistochemical method was used to examine tumor necrosis factor (TNF-α) and lung tissue lung surface active substances related proteins A (SP-A) of rats at different points after surgery.@*RESULTS@#There was no significant differences in the expression of TNF-α at 6 hours, 3 days, and 7 days after surgery in the 5 groups (P>0.05). The expression of TNF-α in Group D, and E was significantly higher than that in Group A at 1 day after surgery (P Group D > Group C > Group B at 1 day, 3 days after surgery, there was no significant difference among the 4 groups. There was no significant differences in the expression of SP-A at 6 hours, 3 days, and 7 days after surgery in the 5 groups (P>0.05). The expression of SP-A in Group D and E was significantly higher than that in Group A at 1 day after surgery (P0.05).@*CONCLUSION@#The greater the stimulant intensity of abdominal operation on rats, the more impact on postoperative lung. The postoperative pulmonary effect of intraperitoneal operation is greater than non-intraperitoneal operation, but in the compensation.


Subject(s)
Anesthesia , Animals , Digestive System Surgical Procedures , Laparoscopy , Lung , Metabolism , Male , Postoperative Period , Propofol , Pulmonary Surfactant-Associated Protein A , Metabolism , Rats , Rats, Sprague-Dawley , Surface-Active Agents , Tumor Necrosis Factor-alpha , Metabolism
10.
Article in Chinese | WPRIM | ID: wpr-345664

ABSTRACT

<p><b>OBJECTIVE</b>To study the variation and clinical significance of serum levels of surfactant proteins A (SP-A) and D (SP-D) among children with different degrees of bronchiolitis.</p><p><b>METHODS</b>Seventy children with bronchiolitis were divided into acute (n=42) and recovery phase groups (n=28). According to the severity of symptoms, the acute phase group was further divided into severe (n=12) and mild subgroups (n=30). Another 26 children who were hospitalized in the same period due to non-infectious diseases and had not undergone surgery were used as the control group. Competitive enzyme-linked immunosorbent assay was performed to measure serum levels of SP-A and SP-D in each group.</p><p><b>RESULTS</b>The acute phase group had significantly higher serum levels of SP-A and SP-D compared with the recovery phase (P<0.01) and control groups (P<0.01). Compared with the control group, the recovery phase group had elevated levels of SP-A and SP-D (P<0.01). Within the acute phase group, serum levels of SP-A and SP-D in the severe subgroup were significantly higher than in the mild subgroup (P<0.01).</p><p><b>CONCLUSIONS</b>Serum levels of SP-A and SP-D are significantly elevated in children with acute bronchiolitis, and severe cases have higher serum levels of SP-A and SP-D than mild cases. Even after the relief of clinical symptoms, serum levels of SP-A and SP-D remain high. These findings suggest that serum levels of SP-A and SP-D might be useful biomarkers for evaluating the severity of bronchiolitis among children.</p>


Subject(s)
Acute Disease , Biomarkers , Bronchiolitis , Blood , Female , Humans , Infant , Male , Pulmonary Surfactant-Associated Protein A , Blood , Pulmonary Surfactant-Associated Protein D , Blood , Severity of Illness Index
11.
Yonsei Medical Journal ; : 1422-1429, 2013.
Article in English | WPRIM | ID: wpr-100957

ABSTRACT

PURPOSE: Recently, Forkhead box M1 (FoxM1) was reported to be correlated with lung maturation and expression of surfactant proteins (SPs) in mice models. However, no study has been conducted in rabbit lungs despite their high homology with human lungs. Thus, we attempted to investigate serial changes in the expressions of FoxM1 and SP-A/B throughout lung maturation in rabbit fetuses. MATERIALS AND METHODS: Pregnant New Zealand White rabbits were grouped according to gestational age from 5 days before to 2 days after the day of expected full term delivery (F5, F4, F3, F2, F1, F0, P1, and P2). A total of 64 fetuses were enrolled after Cesarean sections. The expressions of mRNA and proteins of FoxM1 and SP-A/B in fetal lung tissue were tested by quantitative reverse-transcriptase real-time PCR and Western blot. Furthermore, their correlations were analyzed. RESULTS: The mRNA expression of SP-A/B showed an increasing tendency positively correlated with gestational age, while the expression of FoxM1 mRNA and protein decreased from F5 to F0. A significant negative correlation was found between the expression levels of FoxM1 and SP-A/B (SP-A: R=-0.517, p=0.001; SP-B: R=-0.615, p<0.001). CONCLUSION: Preterm rabbits demonstrated high expression of FoxM1 mRNA and protein in the lungs compared to full term rabbits. Also, the expression of SP-A/B was inversely related with serial changes in FoxM1 expression. This is the first report to suggest an association between FoxM1 and expression of SP-A/B and lung maturation in preterm rabbits.


Subject(s)
Animals , Blotting, Western , Female , Fetus/metabolism , Forkhead Transcription Factors/metabolism , Lung/metabolism , Pregnancy , Pulmonary Surfactant-Associated Protein A/genetics , Rabbits
12.
Chinese Journal of Pediatrics ; (12): 779-782, 2013.
Article in Chinese | WPRIM | ID: wpr-275623

ABSTRACT

<p><b>OBJECTIVE</b>To study the alterations and relationship of surfactant protein (SP)-A, SP-D and KL-6 in serum and bronchoalveolar lavage fluids (BALF) in children with Mycoplasma pneumoniae pneumonia (MPP).</p><p><b>METHOD</b>Self-control method was used for the study on SP-A, SP-D and KL-6 in serum, infected and non-infected BALFs in 32 MMP children with only one side of MPP.</p><p><b>RESULT</b>The contents of SP-A, SP-D and KL-6 in infected BALF were [mg/L;M (IQR) ]: 243 (90-468) , 187 (43-333) , 148 (47-426) ;104 (37-257) , 56 (25-131) , 35 (12-147) in non-infected BALF; 35 (25-69) , 33 (9-149) and 24 (15-62) in serum. The correlation coefficient of KL-6 between serum and infected BALF were -0.534 and -0.378 (P < 0.05).</p><p><b>CONCLUSION</b>There were significant correlation between the alterations of SP-A, SP-D and KL-6 in serum and lung infection in children with CAP. KL-6 in serum may be more sensitive than SP-A and SP-D.</p>


Subject(s)
Adolescent , Biomarkers , Blood , Metabolism , Bronchoalveolar Lavage Fluid , Chemistry , Child , Child, Preschool , Female , Humans , Infant , Lung , Metabolism , Pathology , Male , Mucin-1 , Blood , Metabolism , Pneumonia, Mycoplasma , Blood , Metabolism , Pulmonary Surfactant-Associated Protein A , Blood , Metabolism , Pulmonary Surfactant-Associated Protein D , Blood , Metabolism , Severity of Illness Index
13.
Chinese Medical Journal ; (24): 1945-1951, 2012.
Article in English | WPRIM | ID: wpr-283688

ABSTRACT

<p><b>BACKGROUND</b>Idiopathic pulmonary fibrosis (IPF) is a chronic inflammatory interstitial lung disease with an unknown cause. Recent studies have shown that genetic factors play an important role in the pathogenesis of IPF.</p><p><b>METHODS</b>To explore the genetic background of patients with IPF, a candidate gene approach was employed to screen for mutations in seven genes among members with familial IPF in mainland of China.</p><p><b>RESULTS</b>Within six of the candidate genes, a total of 31 point mutations were identified. Among the missense mutations, the SFTPA1 exon 6 CAG > AAG (Gln238Lys) and SFTPB exon 2 CAC > CCC (His2Pro) mutations caused changes in the physical and chemical properties of amino acids. Each sequence alteration was identified in sporadic IPF patients, control specimens (pneumonia patients and healthy persons). Genotype frequencies and allele frequencies of codon 238 in exon 6 of SFTPA1 were noted significantly higher in patients with IPF than those in other two control subjects. The computational protein structure prediction by protein homology modeling confirmed differences in three-dimensional structure between mutant SFTPA1 and original SFTPA1.</p><p><b>CONCLUSIONS</b>Although the functions of the mutant candidate genes vary, these genes may ultimately result in damage to alveolar epithelial cells, initiating the progress of pulmonary fibrosis. In particular, while pathophysiological mechanisms need to be illustrated, the Gln238Lys missense variant of exon 6 in the SFTPA1 may have potential susceptibility in the development of IPF, which was shown in patients with sporadic IPF with a statistically higher frequency.</p>


Subject(s)
Adult , China , Exons , Genetics , Female , Gene Frequency , Genetics , Genetic Predisposition to Disease , Genetics , Genotype , Humans , Idiopathic Pulmonary Fibrosis , Genetics , Male , Mutation , Genetics , Mutation, Missense , Genetics , Pulmonary Surfactant-Associated Protein A , Genetics
14.
Article in Chinese | WPRIM | ID: wpr-339591

ABSTRACT

<p><b>OBJECTIVE</b>This study examined the effects of maternal deficiency of folic acid during pregnancy on pulmonary development and protein A (SP-A) expression in newborn rats in order to explore the possible mechanism of lung developmental disorders.</p><p><b>METHODS</b>Thirty-six adult Sprague-Dawley female rats were randomly assigned into two groups: control and study (n=18). The study and the control groups were fed with fodder containing folic acid or not respectively. Two weeks later, the female rats in the two groups copulated with normal male rats. Newborn rats were sacrificed at 1, 7 and 14 days after birth (8 pups at each time point). Lung sections were stained with hematoxylin and eosin for histological examination. SP-A expression of protein and mRNA were determined by immunohistochemistry and real-time quantitative RT-PCR, respectively.</p><p><b>RESULTS</b>The newborn rats from the study group showed damaged lung tissue structures. The mean optical density of type II cells with positive expression of SP-A decreased significantly from 1 to 14 days in newborn rats of the study group compared with the control newborn rats (P<0.05). The real-time quantitative RT-PCR showed that the expression of lung SP-A mRNA also decreased significantly from 1 to 14 days in newborn rats of the study group compared with control newborn rats (P<0.05).</p><p><b>CONCLUSIONS</b>Maternal deficiency of folic acid during pregnancy can decrease the expression of SP-A in lung tissues of newborn rats, which might lead to the disorder of lung development maturation.</p>


Subject(s)
Animals , Animals, Newborn , Female , Folic Acid Deficiency , Metabolism , Immunohistochemistry , Lung , Embryology , Male , Pregnancy , Pregnancy Complications , Metabolism , Pulmonary Surfactant-Associated Protein A , Genetics , RNA, Messenger , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction
15.
Article in Chinese | WPRIM | ID: wpr-347575

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the expression of interleukin 8 (IL-8), surfactant protein-A (SP-A) and transforming growth factor beta1 (TGF-beta1) in bronchoalveolar lavage fluid (BALF) of neonates with bronchopulmonary dysplasia (BPD).</p><p><b>METHODS</b>Thirty neonates with BPD and 30 gestational age-, gender-, and birth weight-matched neonates without BPD (control group) were enrolled from December 2007 to October 2009. Non-brochoscopic bronchoalveolar lavage was performed. The levels of IL-8, SP-A and TGF-beta1 in BALF were measured using ELISA.</p><p><b>RESULTS</b>The levels of TGF beta1 (47+/-15 microg/mL vs 34+/-13 microg/mL) and IL-8 (54+/-16 microg/mL vs 28+/-13 microg/mL) in the BPD group were significantly higher than those in the control group (P<0.01). In contrast, the contents of SP-A in the BPD group were significantly lower than those in the control group (35+/-16 microg/mL vs 42+/-14 microg/mL;P<0.05).</p><p><b>CONCLUSIONS</b>The increased expression of TGF-beta1 and IL-8 in BALF may be involved in abnormal lung development and maturation in neonates with BPD. The low expression of SP-A in the BPD group suggests that the exogenous SP-A administration may be an option for the treatment of BPD.</p>


Subject(s)
Bronchoalveolar Lavage Fluid , Chemistry , Bronchopulmonary Dysplasia , Metabolism , Enzyme-Linked Immunosorbent Assay , Female , Humans , Infant, Newborn , Interleukin-8 , Physiology , Male , Pulmonary Surfactant-Associated Protein A , Physiology , Transforming Growth Factor beta1 , Physiology
16.
Protein & Cell ; (12): 188-197, 2010.
Article in English | WPRIM | ID: wpr-757716

ABSTRACT

The role of surfactant protein A (SP-A) in the recognition and clearance of apoptotic cells is well established, but to date, it is still not clear which surface molecules of apoptotic cells are involved in the process. Here we present evidence that phosphatidylserine (PS) is a relevant binding molecule for human SP-A. The binding is Ca(2+)-dependent and is not inhibited by mannose, suggesting that the sugar-binding site of the carbohydrate recognition domain (CRD) of SP-A is not involved. Flow cytometry studies on apoptotic Jurkat cells revealed apparent inhibition of annexin V binding by increasing concentrations of SP-A in late apoptotic but not early apoptotic cells, and this was consistent for Jurkat cells and neutrophils. Supporting these data, confocal microscopy results show a co-localisation of annexin V and SP-A in late apoptotic but not early apoptotic cells. However, we cannot conclude that this inhibition is exclusively due to the binding of SP-A to PS on the cell surface, as annexin V is not wholly specific for PS and SP-A also interacts with other phospholipids that might become exposed on the apoptotic cell surface.


Subject(s)
Annexin A5 , Metabolism , Apoptosis , Carboxy-Lyases , Metabolism , Flow Cytometry , Humans , Jurkat Cells , Microscopy, Confocal , Neutrophils , Physiology , Phosphatidylserines , Metabolism , Pulmonary Surfactant-Associated Protein A , Metabolism
17.
Protein & Cell ; (12): 563-572, 2010.
Article in English | WPRIM | ID: wpr-757695

ABSTRACT

Surfactant proteins A (SP-A) and D (SP-D), both members of the collectin family, play a well established role in apoptotic cell recognition and clearance. Recent in vitro data show that SP-A and SP-D interact with apoptotic neutrophils in a distinct manner. SP-A and SP-D bind in a Ca(2+)-dependent manner to viable and early apoptotic neutrophils whereas the much greater interaction with late apoptotic neutrophils is Ca(2+)-independent. Cell surface molecules on the apoptotic target cells responsible for these interactions had not been identified and this study was done to find candidate target molecules. Myeloperoxidase (MPO), a specific intracellular defense molecule of neutrophils that becomes exposed on the outside of the cell upon apoptosis, was identified by affinity purification, mass-spectrometry and western blotting as a novel binding molecule for SP-A and SP-D. To confirm its role in recognition, it was shown that purified immobilised MPO binds SP-A and SP-D, and that MPO is surface-exposed on late apoptotic neutrophils. SP-A and SP-D inhibit binding of an anti-MPO monoclonal Ab to late apoptotic cells. Fluorescence microscopy confirmed that anti-MPO mAb and SP-A/SP-D colocalise on late apoptotic neutrophils. Desmoplakin was identified as a further potential ligand for SP-A, and neutrophil defensin as a target for both proteins.


Subject(s)
Apoptosis , Binding, Competitive , Fluorescent Antibody Technique, Indirect , Humans , Neutrophils , Chemistry , Cell Biology , Metabolism , Peroxidase , Metabolism , Protein Binding , Pulmonary Surfactant-Associated Protein A , Metabolism , Pulmonary Surfactant-Associated Protein D , Metabolism
18.
Article in Chinese | WPRIM | ID: wpr-254885

ABSTRACT

<p><b>OBJECTIVE</b>To explore the mechanism of acupuncture for treatment of asthma.</p><p><b>METHODS</b>Forty SD rats were randomly divided into 5 groups: blank control group, normal saline control group (NS control group), asthma model group, asthma model with acupuncture group (asthma acupuncture group) and asthma model with binding group (asthma binding group). The asthma acupuncture group was treated with acupuncture at "Dazhui" (GV 14), "Feishu" (BL 13) and "Fengmen" (BL 12); the asthma binding group was only binding without acupuncture and no intervention was given in the other groups. Surfactant protein-A (SP-A) expression was examined by Western-Blot.</p><p><b>RESULTS</b>Airway resistance in asthma model group was significantly higher than that in blank control group and NS control group from 3 to 6 min after asthma provocation (all P<0.01). Western-Blot detection showed that SP-A expression in bronchoalveolar lavage fluid (BALF) of the rats in asthma model group was significantly lower than that in blank control group and NS control group (both P<0.05), and which in asthma acupuncture group was significantly higher than that in asthma model group (P<0.05).</p><p><b>CONCLUSION</b>The mechanism of prevention and treatment of acupuncture for allergic asthma is related to regulating SP-A expression of airway in asthmatic rats.</p>


Subject(s)
Acupuncture Therapy , Animals , Asthma , Genetics , Allergy and Immunology , Therapeutics , Bronchoalveolar Lavage Fluid , Allergy and Immunology , Disease Models, Animal , Gene Expression , Humans , Male , Pulmonary Surfactant-Associated Protein A , Genetics , Allergy and Immunology , Random Allocation , Rats , Rats, Sprague-Dawley
19.
Chinese Medical Journal ; (24): 726-729, 2010.
Article in English | WPRIM | ID: wpr-242582

ABSTRACT

<p><b>BACKGROUND</b>Liver fibrosis is the process through which numerous chronic liver diseases develop into liver cirrhosis. Leptin can activate hepatic stellate cells (HSCs) and play an important role in the formation of liver fibrosis. However, the process by which leptin activates HSCs is complicated, and research on this process is limited. The aim of this study was to explore the related changes in gene expression and the control mechanisms involved in leptin activated HSCs to understand the overall mechanism of liver fibrosis development.</p><p><b>METHODS</b>We cultivate rat HSCs, with and without stimulation by leptin, and extracted mRNA. Differentially expressed genes were detected by microarray analysis.</p><p><b>RESULTS</b>The differentially expressed genes identified included six upregulated genes and six downregulated genes. The representative upregulated genes included short chain dehydrogenase (CY5/CY3 = 2.265) and pulmonary surfactant protein A1 (CY5/CY3 = 2.036). The significant downregulated gene encoded hepatic stearoyl coenzyme A desaturase 1 (SCD-1) (CY5/CY3 = 0.351).</p><p><b>CONCLUSION</b>Leptin might mediate the molecular biological mechanisms of liver fibrosis.</p>


Subject(s)
Animals , Cells, Cultured , Gene Expression Profiling , Hepatic Stellate Cells , Metabolism , Leptin , Pharmacology , Oligonucleotide Array Sequence Analysis , Methods , Pulmonary Surfactant-Associated Protein A , Genetics , Rats , Stearoyl-CoA Desaturase , Genetics
20.
Article in Chinese | WPRIM | ID: wpr-747934

ABSTRACT

OBJECTIVE@#To detect the expression and distribution of surfactant A (SP-A) in nasal polyps and to probe into its significance in the pathology of nasal polyps.@*METHOD@#Immunohistochemical staining and RT-PCR (reverse transcription polymerase chain reaction) were explored to detect SP-A in nasal polyps and controls.@*RESULT@#In nasal polyp tissues, SP-A expressed not only in the cytoplasm of the epithelium but also in the cytoplasm of the plasma cells. Moreover it expressed in the serous glands but not in the mucous glands. The expression of SP-A was distributed in the same location of turbinates. But the expression of SP-A between nasal polyps and turbinates differed significantly (P < 0.05). SP-A mRNA was detected in the nasal polyps and controls. The expression potency ratio of SP-A/beta-actin in nasal polyps was stronger than in turbinates (P < 0.05).@*CONCLUSION@#Both nasal polyps and nasal mucosa expressed SP-A mRNA and protein, but the expression was stronger in nasal polyps. The role of SP-A in the innate immunity may contribute to the pathogenesis of nasal polyps. SP-A may become the new target in the therapy of chronic rhinosinusitis.


Subject(s)
Adult , Aged , Chronic Disease , Female , Humans , Male , Middle Aged , Nasal Mucosa , Metabolism , Nasal Polyps , Metabolism , Pathology , Pulmonary Surfactant-Associated Protein A , Metabolism , Sinusitis , Metabolism , Pathology , Young Adult
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